“Inflammation is an important mediator of secondary neurological injury after traumatic brain injury (TBI). Endocannabinoids, endogenously produced arachidonate based lipids, have recently emerged as powerful anti-inflammatory compounds, yet the molecular and cellular mechanisms underlying these effects are poorly defined. Endocannabinoids are physiological ligands for two known cannabinoid receptors, CB1R and CB2R. In the present study, we hypothesized that selective activation of CB2R attenuates neuroinflammation and reduces neurovascular injury after TBI. Taken together, our findings support the development of selective CB2R agonists as a therapeutic strategy to improve TBI outcomes while avoiding the psychoactive effects of CB1R activation.” https://www.ncbi.nlm.nih.gov/pubmed/29079445 http://www.sciencedirect.com/science/article/pii/S0889159117304774
“The Cannabinoid CB2 Receptor as a Target for Inflammation-Dependent Neurodegeneration. The first approved cannabinoid drugs were analogues of Δ9-tetrahydrocannabinol (Δ9-THC). Dronabinol is a natural isomer of THC that is found in the cannabis plant” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2435344/
“Cannabinoid Receptor CB2 Is Involved in Tetrahydrocannabinol-Induced Anti-Inflammation against Lipopolysaccharide in MG-63 Cells. These results suggested that CB2 is involved in the THC-induced anti-inflammation” https://www.hindawi.com/journals/mi/2015/362126/
“Cannabinoids as novel anti-inflammatory drugs. Manipulation of endocannabinoids and/or use of exogenous cannabinoids in vivo can constitute a potent treatment modality against inflammatory disorders. For several centuries, marijuana has been used as an alternative medicine in many cultures and, recently, its beneficial effects have been shown” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2828614/
“Cannabinoids as neuroprotective agents in traumatic brain injury. Cannabinoids of all classes have the ability to protect neurons from a variety of insults that are believed to underlie delayed neuronal death after traumatic brain injury (TBI), including excitotoxicity, calcium influx, free radical formation and neuroinflammation.” https://www.ncbi.nlm.nih.gov/pubmed/15281893
“Effect of marijuana use on outcomes in traumatic brain injury. A positive THC screen is associated with decreased mortality in adult patients sustaining TBI.” https://www.ncbi.nlm.nih.gov/pubmed/25264643
“Stroke is a neurological disease, which, in addition to high mortality, imposes many financial and mental burdens on families and the society.
The main objective of this study was to investigate the effect of cannabidiol (CBD) on one of the major inflammatory pathways in cerebral ischaemia.
Administration of CBD (100 and 200 ng/rat) caused a significant reduction in infarction, brain oedema, and BBB permeability compared with the vehicle-received group. Down-regulation of TNF-α, TNFR1, and NF-кB expression was also observed by CBD.
The results achieved in this study support the idea that CBD has a cerebroprotective effect (partly through suppression of TNF-α, TNFR1, and NF-кB) on ischaemic injury.”
“Brain hypoxic-ischemic (HI) damage induces distant inflammatory lung damage in newborn pigs. We aimed to investigate the effects of cannabidiol (CBD) on lung damage in this scenario.
CBD prevented HI-induced deleterious effects on TLC and OI and reduced lung histological damage, modulating inflammation (decreased leukocyte infiltration and IL-1 concentration) and reducing protein content in BALF and EVLW. These effects were related to CBD-induced anti-inflammatory changes in the brain. HI did not increase oxidative stress in the lungs. In the lungs, WAY100635 blunted CBD’s beneficial effects on histological damage, IL-1 concentration and EVLW.
CBD reduced brain HI-induced distant lung damage, with 5-HT1A receptor involvement in these effects. Whether CBD’s effects on lungs were due to anti-inflammatory effects on the brain or to direct effects on lungs remains to be elucidated.” https://www.ncbi.nlm.nih.gov/pubmed/28388598
“Hypoxic-ischemic brain injury is a diagnostic term that encompasses a complex constellation of pathophysiological and molecular injuries to the brain induced by hypoxia, ischemia, cytotoxicity, or combinations of these conditions. The typical causes of hypoxic-ischemic brain injury – cardiac arrest, respiratory arrest, near-drowning, near-hanging, and other forms of incomplete suffocation, carbon monoxide and other poisonous gas exposures, and perinatal asphyxia – expose the entire brain to potentially injurious reductions of oxygen (i.e., hypoxia) and/or diminished blood supply (ischemia).” http://www.internationalbrain.org/articles/hypoxicischemic-brain-injury/
“Hypoxic-ischemic brain damage induces distant inflammatory lung injury in newborn piglets.” https://www.ncbi.nlm.nih.gov/pubmed/25950454
“Cannabidiol reduces lung injury induced by hypoxic-ischemic brain damage in newborn piglets.” https://www.ncbi.nlm.nih.gov/pubmed/28388598
“Nearly half of all states have legalized medical marijuana or recreational-use marijuana. As more states move toward legalization, the effects on injured patients must be evaluated.
This study sought to determine effects of cannabis positivity at the time of severe injury on hospital outcomes compared with individuals negative for illicit substances and those who were users of other illicit substances.
Cannabis users suffering from severe injury demonstrated no detrimental outcomes in this study compared with nondrug users.”
“The major endocannabinoid in the mammalian brain is the bioactive lipid 2-arachidonoylglycerol (2-AG). The best-known effects of 2-AG are mediated by G-protein-coupled cannabinoid receptors. In principle, 2-AG could modify neuronal excitability by acting directly on ion channels, but such mechanisms are poorly understood.
Using a preparation of dissociated mouse midbrain dopamine neurons to isolate effects on intrinsic excitability, we found that 100 nM 2-AG accelerated pacemaking and steepened the frequency-current relationship for burst-like firing. In voltage-clamp experiments, 2-AG reduced A-type potassium current (IA) through a cannabinoid receptor-independent mechanism mimicked by arachidonic acid, which has no activity on cannabinoid receptors. Activation of orexin, neurotensin, and metabotropic glutamate Gq/11-linked receptors mimicked the effects of exogenous 2-AG and their actions were prevented by inhibiting the 2-AG-synthesizing enzyme diacylglycerol lipase α.
The results show that 2-AG and related lipid signaling molecules can directly tune neuronal excitability in a cell-autonomous manner by modulating IA.”